Evidence map›Paper›PMID 40855324›Full record

ArticleJournal of translational medicine2025

Sodium-glucose cotransporter 2 inhibitors alleviate renal fibrosis in diabetic kidney disease by inhibiting Hmgcs2 and Btg2 in proximal tubular cells.

Shengzhe Yan, Minhui Luo, Rui Zhou, Fenfen Peng, Mingze Zhang, Yujie Feng, Liang Zhao, Li Yang, Yanzhen Cheng

Abstract read
In one paragraph

Article in Journal of translational medicine, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.

0numbers the graph read from it
0cells of the map it votes in
3citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

3 citing papers in PubMed.

  1. Research progress on BTG2 in non‑tumor diseases (Review).International journal of molecular medicine · 2026
    Review
  2. Review
  3. Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

9 authors.

Shengzhe Yan *Department of Endocrinology, Zhujiang Hospital, Southern Medical University, Guangzhou, Guangdong, China.ORCID 0000-0001-6827-5228
Minhui Luo *Department of Endocrinology, Zhujiang Hospital, Southern Medical University, Guangzhou, Guangdong, China.
Rui Zhou *Department of Pathology, School of Basic Medical Sciences, Southern Medical University, Guangzhou, Guangdong, China.
Fenfen PengDepartment of Nephrology, Zhujiang Hospital, Southern Medical University, Guangzhou, Guangdong, China.
Mingze ZhangDepartment of Endocrinology, Zhujiang Hospital, Southern Medical University, Guangzhou, Guangdong, China.
Yujie FengDepartment of Endocrinology, Zhujiang Hospital, Southern Medical University, Guangzhou, Guangdong, China.
Liang ZhaoDepartment of Pathology, School of Basic Medical Sciences, Southern Medical University, Guangzhou, Guangdong, China. liangsmu@foxmail.com.
Li YangDepartment of Endocrinology, Zhujiang Hospital, Southern Medical University, Guangzhou, Guangdong, China. yangli19762009@163.com.
Yanzhen ChengDepartment of Endocrinology, Zhujiang Hospital, Southern Medical University, Guangzhou, Guangdong, China. chengyzx@163.com.

Funding

National Natural Science Foundation of China 82170796Science and Technology Planning Project of Guangdong Province 2022A0505030005
6 · The paper itself

Abstract

contextSodium-glucose cotransporter 2 inhibitors (SGLT2i) have been shown to ameliorate renal fibrosis in diabetic kidney disease (DKD), but the mechanism has not been fully explored.

methodsThe single-cell sequencing (scRNA-seq) data were downloaded from the Gene Expression Omnibus (GEO) database, and we selected the tissue data from db/m mice, db/db mice and db/db mice with SGLT2i treatment. The results were also validated by immunofluorescent staining and western blot in vivo and in vitro, respectively.

resultsOur study demonstrates that SGLT2i directly ameliorated fibrosis of proximal tubular cells by downregulating 3-hydroxy-3-methylglutaryl-CoA synthase 2 (Hmgcs2) expression in S1 proximal tubular segment cells (PT_S1) and decreasing the number of proximal tubular cell cluster with B-cell translocation gene 2 (Btg2) highly expressed (Btg2_PT). In addition, SGLT2i could indirectly influence macrophages through cell-cell communication between epithelial cells and macrophages, specifically via the App-CD74 ligand-receptor pair, thus suppressing the inflammatory response in macrophages, ultimately contributing to the delay in DKD progression.

conclusionOur study found that Hmgcs2 and Btg2 are therapeutic targets for Sodium-glucose cotransporter 2 inhibitors to ameliorate kidney fibrosis in diabetic kidney disease. Single-cell sequencing technology provided a high resolution of this study at the cellular level.

Indexed as

Diabetic NephropathiesHydroxymethylglutaryl-CoA SynthaseImmediate-Early ProteinsKidney Tubules, ProximalSodium-Glucose Transporter 2 InhibitorsTumor Suppressor ProteinsAnimalsFibrosisMacrophagesMaleMiceSodium-Glucose Transporter 2Hydroxymethylglutaryl-CoA SynthaseImmediate-Early ProteinsSodium-Glucose Transporter 2Sodium-Glucose Transporter 2 InhibitorsTumor Suppressor ProteinsBtg2Diabetic kidney diseaseHmgcs2Renal fibrosisSGLT2iSingle-cell sequencing

Identifiers

PMID40855324
PMCPMC12379496

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.